Dep. of Cellular Biotechnology, and Ematology, University of Rome La Sapienza, Italy.
Neurosci Lett. 2010 Mar 8;471(3):185-8. doi: 10.1016/j.neulet.2010.01.038. Epub 2010 Jan 28.
RNA-Induced Silencing Complex (RISC) mediates post-transcriptional control of gene expression and contains Argonaute 2 (AGO2) protein as a central effector of cleavage or inhibition of mRNA translation. In the brain, the RISC pathway is involved in neuronal functions, such as synaptic development and local protein synthesis, which are potentially critical for memory. In this study, we examined the role of RISC in memory formation in rodents, by silencing AGO2 expression in dorsal hippocampus of C57BL/6 mice and submitting animals to hippocampus-related tasks. One week after surgery, AGO2 downregulation impaired both short-term and long-term contextual fear memories. Conversely, no long-lasting effects were observed three weeks after surgery, when AGO2 levels were re-established. These results show that altered RISC activity severely affects learning and memory processes in rodents.
RNA 诱导沉默复合物（RISC）介导基因表达的转录后调控，包含 Argonaute 2（AGO2）蛋白作为切割或抑制 mRNA 翻译的核心效应因子。在大脑中，RISC 途径参与神经元功能，如突触发育和局部蛋白质合成，这对记忆可能至关重要。在这项研究中，我们通过在 C57BL/6 小鼠的背侧海马体中沉默 AGO2 的表达，并使动物接受与海马体相关的任务，来研究 RISC 在啮齿动物记忆形成中的作用。手术后一周，AGO2 的下调损害了短期和长期的情境恐惧记忆。相反，在手术后三周时，当 AGO2 水平恢复时，没有观察到持久的影响。这些结果表明，改变的 RISC 活性严重影响了啮齿动物的学习和记忆过程。
